Search PubMed⌕ Search

Biomedical subjects

L Goldstein

Publications and source records attributed to L Goldstein.

At least 145 records · Page 8Linked to original sources
PubMed1986

Taurine transport by the flounder (Pseudopleuronectes americanus) intestine.

Taurine transport by the flounder gut was characterized in isolated strips of intestine mounted between Ringer's solutions. Taurine was transported into the cell, against its concentration gradient, by a sodium-dependent system present in both the mucosal and serosal membranes. This system appears to be specific for beta-amino acids and is regulated by cyclic nucleotides (cGMP and cAMP). Kinetic analyses indicated that under physiological conditions the magnitudes of the bidirectional taurine uptake rates would favor net absorption of taurine from lumen to blood.

Animals↗
PubMed1986

Antiviral and antitumor effects of a human interferon analog, IFN-alpha Con 1, assessed in hamsters.

An analog of human alpha-and beta-interferons (IFN-alpha and -beta) (generally consisting of the most frequently observed amino acid residue at each position in the molecule) has pronounced antiviral and antiproliferative activity in human and hamster cells. Intraperitoneal administration of this analog (designated IFN-alpha Con 1) to hamsters at 10(6) to 10(8) U/kg resulted in proportional increases in plasma concentrations through 6 h of monitoring. IFN-alpha Con 1 at these doses effectively limited encephalomyocarditis virus (EMCV) infections of hamsters. A natural human IFN-alpha preparation was also active against virus infections in hamsters. The antitumor activity of IFN-alpha Con 1 and natural human IFN-alpha was assessed in hamsters inoculated with lethal TBD932 lymphosarcoma. Various IFN treatment schedules resulted in prolonged survival following tumor challenge. IFN-alpha Con 1 administered at 10(5) to 10(6) U/hamster daily for 9-12 days following tumor challenge was effective in delaying tumor development, as was a natural human IFN-alpha preparation. The efficacies of combined IFN and cyclophosphamide therapies were determined. Unlike the natural human subtype IFN-alpha A, IFN-alpha Con 1 did not diminish the efficacy of cyclophosphamide (2.5 mg/hamster for 3 days) against the lymphosarcoma. However, an ineffective dose of cyclophosphamide (0.05 mg/hamster for 3 days) when combined with IFN-alpha Con 1 treatment showed enhanced antitumor activity. Combinations of cimetidine (16 mg/hamster for 4 days) and IFN-alpha Con 1 treatment did not prolong survival in this model system.

Animals↗
PubMed1986

Ionic requirements of peritubular taurine transport in Fundulus kidney.

A peritubular mechanism for active taurine uptake, similar to that previously found in the flounder, was demonstrated in killifish (Fundulus heteroclitus) teased renal tubules. Other beta-amino acids and glycine inhibited taurine transport. Uptake exhibited a nearly absolute requirement for external Na+. The stoichiometric relationship between Na+ and taurine was found to be 2:1. Medium Cl- markedly stimulated the Na+-dependent taurine uptake, but none of the other small monovalent anions tested (NO3-, Br-, SCN-) could substitute for Cl- in activating taurine transport. Cl- replacement resulted in a significant decrease in V max, whereas the affinity of the carrier for taurine appeared to be unaffected. In the absence of Cl- the Na+ dependence of taurine influx was reduced to a stoichiometric relationship of 1.4 Na+:1 taurine, indicating an effect of Cl- on the binding of Na+ to the transport system. A model for Na+ -Cl- -taurine cotransport is presented.

Animals↗
PubMed1985

Differential action of six human interferons against two human carcinomas growing in nude mice.

Six different pure human interferons (IFNs), were tested for anti-tumour effect against two human carcinomas, breast and bowel, growing in nude mice, in a total of 36 experiments. The IFN-alpha mixture, analogue and subtypes showed the greatest activity, particularly against the breast cancer xenograft, whereas IFN-beta and IFN-gamma had little effect. However, circulating IFN could be found in the sera of mice treated with all 3 IFN types. In terms of amount of IFN protein, IFN-alpha Con1, an IFN-alpha analogue, was the most effective, a dose of 0.1 micrograms/mouse/day being sufficient to induce breast tumour regression, and IFN-gamma the least effective, a dose of 10 micrograms/mouse/day having no effect on the same tumour. A more detailed comparison of 2 IFN-alpha subtypes showed that a daily dose of 1 microgram IFN-alpha A was more effective than the same dose of IFN-alpha D, but as this IFN had approximately 30 times less antiviral activity on human cells than IFN-alpha D, these IFNs were probably at least equally effective in terms of human cell units. IFN-alpha D stimulated mouse spleen natural killer cell activity but it was not clear whether this stimulation was involved in anti-tumour activity. We conclude that this model system is useful for investigating direct anti-tumour activity of a wide range of IFN types and subtypes.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Membranous obstruction of the inferior vena cava in the United States.

The pathogenesis of membranous obstruction of the inferior vena cava (MOVC) is unclear. Although the lesion is rare in the United States compared to Japan, India, and black South Africa, it has been responsible for 23% of cases of hepatic outflow obstruction we have encountered in the ethnically heterogeneous indigent population of Los Angeles. Most patients with MOVC are male. In contrast, recent series of patients with Budd-Chiari Syndrome (BCS) have demonstrated a female predominance. Compared to BCS without involvement of the inferior vena cava (IVC), patients with MOVC have more chronic symptoms. Large truncal collaterals, particularly on the back, strongly suggest MOVC. In patients without this sign, a high index of diagnostic suspicion is required. Chronic hepatitis B infection occurs with increased frequency in these patients. Chest radiograph may show an enlarged azygous shadow. Liver-spleen scan is not helpful, and the liver biopsy is frequently nondiagnostic. A useful screening procedure for hepatic outflow block is transhepatic portal pressure measurement demonstrating aberrant hepatic veins with pressures higher than in the portal vein and, occasionally, hepatofugal portal flow. Transcardiac membranotomy appears to be symptomatically effective in patients with MOVC and at least one patent hepatic vein. It is not known whether this operation will prolong life and prevent the development of hepatocellular cancer, which may occur in up to 48% of these patients. The correct therapeutic approach has not been established for those patients whose lesion is not amenable to surgery because of extensive IVC occlusion or absence of patent hepatic veins.

Adult↗
PubMed1985

Confirmation of Legionella pneumophila cultures with a fluorescein-labeled monoclonal antibody.

We compared a fluorescein-labeled monoclonal antibody directed against an outer membrane protein of Legionella pneumophila (Genetic Systems Corp. [GSC], Seattle, Wash.) with a similarly labeled polyclonal reagent (L. pneumophila serogroups 1 to 6, poly; BioDx, Inc., Denville, N.J.) for the confirmation of L. pneumophila isolates grown in culture. Duplicate suspensions of 52 organisms, including 21 L. pneumophila and 8 non-L. pneumophila species of legionella, were placed on individual glass slides, fixed, and stained with both reagents, and the results were compared. Both antisera correctly identified all L. pneumophila serogroups 1 to 6, but only the GSC reagent produced definitive staining of the L. pneumophila isolates of serogroups 7, 8, and 9. Additionally, the GSC reagent produced more uniform staining patterns around the legionella bacilli and displayed little background fluorescence when compared with the BioDx reagent.

Antibodies, Bacterial↗
PubMed1985

Renal excretion of nitrogenous compounds in vertebrates.

The renal excretion of nitrogenous compounds plays an important role not only in the elimination of nitrogen end-products but also in regulating the acid-base and osmotic balance of body fluids. The major nitrogenous compounds excreted by the vertebrate kidney are ammonia, urea and uric acid. The present review addresses the renal excretion of these compounds and, in addition, the amino acid taurine. The functions of excretion; the mechanisms of excretion including renal metabolism, renal handling (secretion, reabsorption, and filtration), and transepithelial transport processes; and the factors regulating these mechanisms are discussed. Renal nitrogen excretion among the vertebrate classes from fish to mammals is compared.

Ammonia↗
PubMed1985

Regulation of T cell proliferation by cloned interferon-alpha mediated by Leu-11b-positive cells.

The autologous T lymphocyte proliferative response (AMLR) induced by a B lymphocyte-enriched non-T, nonadherent cell population (NT, NAC) and by a macrophage-enriched population were both suppressed by the addition of a cloned interferon-alpha (IFN-alpha Con1) directly to the cultures. Preincubation of the stimulating NT, NAC with IFN-alpha Con1 resulted in comparable suppression. In contrast, preincubation of the macrophages with IFN-alpha Con1 resulted in significant augmentation of T cell proliferation. Depletion of Leu-11b-positive cells from the NT, NAC exposed to IFN-alpha Con1 restored the autologous T cell response. Addition of IFN-alpha Con1 activated Leu-11b-positive cells, isolated from the NT, NAC population, was suppressive of the AMLR. Although NK cytotoxicity was irradiation sensitive, suppression of the AMLR by IFN-alpha Con1-activated NT, NAC was resistant, suggesting that different subsets of cells or mechanisms by the same cells may have been responsible. These observations may offer insights into the potential role of cells with the NK phenotype, Leu-11b, and IFN in contributing to immuno-regulatory changes observed in clinical states associated with elevated concentrations of IFN.

Antibodies, Monoclonal↗
PubMed1985

Stimulation of in vitro immunoglobulin production by interferon-alpha.

The effect of various natural and recombinant DNA-derived human interferon-alpha (IFN-alpha) on immunoglobulin (Ig) production by human B cells was investigated. The cell populations examined included peripheral blood mononuclear cells (PBMC) and highly purified B cell and helper T cell populations obtained by negative selection by using monoclonal antibodies and a fluorescence-activated cell sorter. In the presence of all forms of IFN-alpha tested, IgG and IgM production by PBMC increased twofold to fourfold. This increase was noted in the absence of pokeweed mitogen (PWM), was not affected by depletion of monocytes, required that IFN-alpha was present early in the culture period, and reached maximal levels around 500 U/ml IFN-alpha. Both IgG and IgM production were affected, but the magnitude of the IgM response was greater. The augmentation of Ig production was noted with the recombinant DNA-derived subtype, IFN-alpha F, two analogs, IFN-alpha Con1 and IFN-alpha Con2, as well as with buffy-coat-derived (leukocyte) IFN-alpha. The recombinant DNA-derived forms of IFN-alpha appeared to differ in their ability to augment Ig production. In the presence of PWM, IFN-alpha Con1 failed to increase Ig production by PBMC. In contrast to these results with PBMC, IFN-alpha Con1 increased the Ig production of purified B cells 10- to 20-fold in the presence of PWM. This increase reached maximal levels around 500 U/ml IFN-alpha Con1. Although purified B cells responded to IFN-alpha and PWM, maximal responses occurred in the presence of low numbers of helper T cells. Cell dilution experiments suggested that the effect observed with purified B cells was the result of the interaction of B cells with residual cells, e.g., helper T cells, remaining in the preparations.

Antibody Formation↗
PubMed1985

Human alpha and gamma interferon analogs in rabbits with herpetic keratitis.

Complete gene synthesis methods have been used to construct analogs of human interferons (IFNs): these include a consensus of the known human IFN-alpha S, designated IFN-alpha Con1 and a variant of human IFN-gamma, designated IFN-gamma 4A. These interferons, in purified form, were used topically against herpes simplex virus type 1 (HSV-1) induced ocular keratitis in rabbits. Eyes pretreated with IFN-alpha Con1 had decreased signs of infection and a lower incidence of HSV-1 positive trigeminal ganglia (3 of 14 positive) compared to the placebo treated (10 of 14 positive). IFN-alpha Con1 was as effective as natural IFN-alpha subtypes on a units basis, despite the very high specific activity of this analog. IFN-gamma 4A used under similar conditions do not result in beneficial effects with treatments beginning 24 or 48 hr before or 4 hr after virus inoculation. Rabbits with confirmed latent HSV infection were treated topically with IFN-alpha Con1 (10(6) units per eye each day) either before or before and after attempts to intentionally reactivate the infection by bilateral iontophoresis of 6-hydroxydopamine plus topical epinephrine treatment of the corneas. These IFN-alpha Con1 treatment regimens along with intentional reactivation during latency did not: (1) lessen the frequency of inducible ocular shedding episodes; (2) alter the mean time of 3-5 days between attempts to reactive latent infection and the appearance of HSV in tears; or (3) significantly change the incidence of HSV-positive trigeminal ganglia (83-100% HSV positive).

Administration, Topical↗
PubMed1985

Assessment of arteriovenous fistulae from pressure and thermal dilution studies: clinical experience in forearm fistulae.

Knowledge of useful fistula flow (UFF), the maximum blood flow available using twin needles within acceptable pressure limits and without recirculation, is essential for the optimal management of patients receiving maintenance hemodialysis or hemofiltration. A technique for the measurement of UFF employing thermal dilution for the detection of recirculation has been developed. Using this technique, 94 studies were carried out in 69 forearm fistulae. UFF exceeded 400 ml/min in 45 fistulae. In these satisfactory fistulae a normal range was defined for basal intrafistula pressures (60 mmHg being the approximate upper limit of normal). Analysis of arterial and venous line pressure recordings with increasing extracorporeal blood flow and knowledge of the presence or absence of recirculation allowed us to define the functional problem in unsatisfactory fistulae. The functional diagnosis was supported in 16 of 24 fistulae by angiography or surgery or both. In all but two of the remainder, satisfactory UFF was obtained by repositioning the patients' needling sites. Fistulae were divided into different clinical groups. Of 35 fistulae which were thought to be clinically acceptable, 7 were found to be unsatisfactory. In 17 fistulae in patients with poor biochemical control, recirculation was detected in 8. Of 11 fistulae reported to produce poor flows on dialysis, 4 had UFF above 400 ml/min. Of 6 fistulae in patients experiencing needling difficulties, 5 had satisfactory UFF. These studies which take only a few minutes and can be carried out immediately preceding a routine dialysis session not only identify unsatisfactory fistulae, but yield valuable diagnostic information in these cases. This has reduced dependence on angiography and has led to more careful selection of patients for surgery.

Arteriovenous Shunt, Surgical↗
PubMed1985

Mechanistic implications of the induction of thermotolerance in Chinese hamster cells by organic solvents.

Several organic solvents were shown to induce thermotolerance. These included: aliphatic alcohols (ethanol to octanol); local anesthetics; dimethyl sulfoxide; and dimethyl formamide. The minimum concentrations of the various alcohols required to induce tolerance were similar to the threshold doses for cytotoxicity. When only intramembrane concentrations were considered (by multiplying by the appropriate membrane:buffer partition coefficient), then the alcohols' threshold dose to induce tolerance was only mildly a function of carbon number. The efficiency increased almost linearly with a membrane dose from propanol to pentanol, but was slightly reduced for octanol. All alcohols induced tolerance rapidly (within a few hours after 30-min exposure), but the thermotolerance ratio decreased with increasing carbon number. Of the three anesthetics examined, lidocaine was a highly efficient inducer, procaine less so, and tetracaine did not induce tolerance even at a concentration mildly cytotoxic. Dimethyl sulfoxide and dimethyl formamide induced tolerance without cytotoxicity, but the kinetics of doing so was different from that seen with the other solvents. Only cells exposed to these water-soluble agents for 18 h or longer showed evidence of induced heat resistance. Our results indicate that membranes likely are the site for the initiation of solvent-induced cell killing and thermotolerance. The minimum dose of induction may be related to the degree of disorder induced by the individual alcohol, but the amount of tolerance induced is inversely related to this. The data on the effects of local anesthetics show that neither their common functional mode of inhibiting nerve transmission nor their similar level of cytotoxicity insures similar efficiency as tolerance inducers. Results with dimethyl sulfoxide and dimethyl formamide suggest that tolerance can be induced by more than one mechanism, or alternately, that a multiple-step mechanism can be activated at different points along this pathway. We also measured heat shock protein synthesis after several treatments; efficient inducers of thermotolerance also induced these proteins.

Alcohols↗
PubMed1984

Beta-alanine transport in the isolated hepatocytes of the elasmobranch Raja erinacea.

Cells were isolated from the liver of the skate and the uptake of beta-alanine followed using [14C]-beta-alanine. The isolated hepatocytes showed good viability, were found to accumulate beta-alanine from the incubation medium, and did so in a manner indicating a transport system involving a saturable carrier. The data for the rate of beta-alanine uptake suggest that this may be a rate-limiting step in the oxidation of the amino acid by the liver. Experiments indicated that the transport system could distinguish beta-alanine from certain structurally similar molecules (L-alanine and taurine, but not gamma-amino butyrate). Cells isolated from fish adapted to a diluted environment (50% seawater) showed no significant change in the uptake rate. However, evidence indicates that, over the range of beta-alanine concentrations occurring in the fish, the uptake rate would be acutely sensitive to small changes in the concentration in the blood, thus forming a self-regulating system for the metabolism of beta-alanine.

Alanine↗